Fig. 6

PBPK/PD analysis of celecoxib and diclofenac pre-treated with rifampicin. PBPK/PD analysis of COX-2 inhibitors following oral administration of 200 mg celecoxib and 100 mg diclofenac with and without a pre-treatment with 600 mg and 450 mg rifampicin q.d. over 5 and 6 days, respectively. a Comparison of key PK parameters between simulated and experimental data. b Simulation of venous blood plasma concentrations in humans c Metabolite analysis showing venous blood plasma concentrations of correspondent metabolites. d PBPK/PD simulations reflecting drug concentrations of celecoxib and diclofenac in venous blood cells, as well as induced changes in PGE2 formation over time. Celecoxib, CEL; diclofenac, DFN; hydroxy, OH; acyl glucuronide, AGLU; carboxy, COOH; rifampicin, RIF; prostaglandin E2, PGE2; once daily, “q.d”